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Model Mice

Our products include original In addition to mice established by the exchangeable gene trap method, we also sell, through licensing agreements, genetically engineered mice established by universities and research institutes. TransGenic Inc has exclusive license to distribute these mouse lines.

Mouse model lines

Model name References Price (tax excluded)
Integrated stress response indicator mouse
(UMAI-Luc mouse)
Scientific Reports 7, 46230 (2017) 1 pair (2 mice) with the license for reproduction
300,000 JPY
Individual mouse
75,000 JPY/mouse

※Prices for profit organization are applied for luciferase indicator mouse lines
Tg type ER stress indicator mouse
(ERAI-Luc mouse)
Nature Medicine 10, 98–102 (2004)
KI type ER stress indicator mouse
(ERAI-Luc mouse)
Oxidative stress indicator mouse
Scientific Reports 2, 229 (2012)
Inflammation indicator mouse
(IDOL mouse)
Scientific Reports 5, 17205 (2015)
Cathepsin E KO mouse Carcinogenesis .35, .714–726, (2014)
Obesity resistant mouse
(Rmi1 trap mouse)
FEBS Journal 277 677–686 (2010)
Eveningness model mouse
(Clockmutant mouse)
Neuroreport 12, 1461-1464 (2001)
Biochem. Biophys. Res. Commun. 298, 198-202 (2002)
Atopic dermatitis model mouse
(IL33 Tg mouse)
PNAS 110, 13921-13926 (2013)

※These mice shall not be used for any purpose other than the internal research.
※These mice shall not be sold or otherwise provided to any third party for any use.
※We ask to users to submit license agreements for purchasing these products.
※We organize “Society for the study with luciferase indicator mouse” and hold annual meeting. Please contact us about the detail.

Integrated stress response Indicator Mouse (UMAI-Luc mouse)

Integrated stress response Indicator Mouse (UMAI-Luc mouse) Integrated stress response (ISR) is associated with various diseases. Activating transcription factor 4 (ATF4) is a translationally activated protein that plays a role in ISR to regulate downstream stress response genes.

ISR Indicator Mouse
In ISR Indicator Mouse (UMAI-Luc mouse) contains UMAI reporter gene, which visualize cells with ISR by luminescence.

UMAI gene
Translation of ATF4 protein is induced by phosphorylation of the eukaryotic initiation factor 2α (eIF2α). ATF4 mRNA contains 2 (or 3) upstream open reading frames (uORFs), so that a low level of phosphorylated eIF2α leads to translational initiation at the first uORF (uORF1) and reinitiation at the second uORF (uORF2). Translational initiation and reinitiation at these uORFs also inhibit the production of ATF4 protein, because the last uORF overlaps with the coding region. However, a high level of phosphorylated eIF2α leads to slow formation of the translational initiation complex and scans through uORF2, resulting in reinitiation at the ORF encoding ATF4 (Fig. A). Phosphorylation of eIF2α is catalyzed by stress kinases, and cellular stresses activate eIF2α. To detect such ISR, UMAI gene in which the coding region of ATF4 is replaced with that of luciferase was constructed. This construct is activated transcriptionally by a constitutive promoter/enhancer and regulated translationally by uORFs (Fig. B). UMAI-Luc mouse shows lower luminescence signal under normal conditions, but higher luminescence signals under stress conditions such as with Leu (-) diet, administration of pIC, tunicamycin and ASN (Fig. C)

This mouse line can be useful to analyze the cellular stresses in living mouse.
ISR Indicator Mouse

< References >
■ Iwawaki, T., Akai, R., Toyoshima, T, Takeda, N., Ishikawa, T., Yamamura, K.  Transgenic mouse model for imaging of ATF4 translational activation-related cellular stress responses in vivo.  Sci. Rep. 7, 46230 (2017)

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ER Stress Indicator Mouse

ER stress is visualized by ERAI gene as whole-body luminescence imaging ER stress
ER (endoplasmic reticulum) stress is a cellular stress related to unfolded protein response. ER stress response is activated in response to an accumulation of unfolded or misfolded proteins in the lumen of the ER. Sustained ER stress causes cell death and is implicated in various neurodegenerative diseases and metabolic syndrome. Also, implication with other diseases such as myocardial infarction and stroke has been suggested.

ER Stress Indicator Mouse
In ER Stress Indicator Mouse (Tg type ERAI-Luc and KI type ERAI-Luc) conatins ERAI reporter gene, which visualize cells with ER stress by luminescence.

ERAI gene
ERAI (ER stress activated indicator) utilizes the mechanisms of XBP1 protein expression under an ER stress response (Fig. A). Without ER stress, XBP1 mRNA keeps an intron. As a result, a truncated XBP1 protein is translated; however, the protein is degraded immediately. In contrast, under ER stress, the intron is removed from the XBP1 mRNA; consequently, active XBP1 protein is generated.

ERAI gene consists of the XBP1 region containing an N-terminal domain and XBP1’s intron and the luciferase cDNA (Fig.B). Under ER stress condition, the intron is removed; subsequently, luciferase protein is translated (Fig.C).

Tg type ERAI-Luc mouse
ERAI gene is driven by CAGGS promoter, expressing systemically.

NI type ERAI-Luc mouse
ERAI gene was knocked in to the Rosa 26 locus with STOP sequence franked by loxP. ERAI expression can be tissue specific by crossing with Cre express mouse. Observation of light signal in targeted tissue is easier by suppression of signal from other tissues.

< References >
■ Iwawaki, T., Akai, R., Kohno, K., Miura, M. A transgenic mouse model for monitoring endoplasmic reticulum stress. Nat Med. 10 98-102 (2004).

< Patent >
■ Patent No. 4446057

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Oxidative Stress Indicator Mouse

OKD48 visualizes oxidative stress by luminescence in whole-body

Oxidative stress
Oxidative stress reflects an imbalance between the production of free radicals and antioxidant defenses. Toxic effects by free radicals and peroxides cause the damage of cells through the oxidation of proteins, lipids, and DNA. Oxidative stress is thought to be involves in various diseases including arteriosclerosis, diabetes, and rheumatism.

Oxidative Stress Indicator Mouse
Oxidative Stress Indicator Mouse (Tg type OKD-Luc mouse) contains the luciferase reporter OKD48 gene which visualize the oxidative stress by luminescence.

OKD48 gene
OKD48 (Keap1 dependent oxidative stress detector that has the best performance in 48 candidates) gene utilizes the mechanism of Nrf2 protein expression under an oxidative stress response (Fig. A). Nrf2 protein is stabilized under oxidative stress condition and localizes in the nucleus. The nuclear Nrf2 protein binds to ARE (antioxidant response element) and stimulates antioxidant response gene expression. Under the normal condition, Nrf2 is ubiquitinated by Keap1 and is brought into the protease degradation pathway. OKD48 consists of Nrf2 ubiquitination domain and luciferase cDNA, which expression is regulated by oxidative stress condition (Fig. B, C).

< References >
■ Oikawa, D., Akai, R., Tokuda, M., Iwawaki, T.
A transgenic mouse model for monitoring endoplasmic reticulum stress.
Sci Rep. 2, 229 (2012).

< Patent >

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Inflammation Indicator Mouse (IDOL mouse)

IDOL visualizes oxidative stress by luminescence in whole-body Inflammation
Inflammation, which is caused by wound, infection of microorganisms, or autoimmune diseases, shows redness, swelling and fever. Chronic inflammation is thought to be involved in aging, cancer, arteriosclerosis, obese and neurodegenerative diseases. During inflammation, various inflammatory cells are infiltrated, and inflammatory factors are involved. One of the important inflammatory factors is IL-1β (interleukin 1 beta).

Inflammation Indicator Mouse
Inflammation Indicator Mouse (Tg type IDOL mouse) contains the IDOL gene, which is a luciferase reporter to detect cells with inflammation by luminescence.

IDOL gene
IDOL (IL-1β based dual operating luciferase) gene utilizes the expression mechanisms of IL-1β mature protein (Fig. A). IL-1β expression is transcriptionally regulated by NFκB. In normal condition, IκB binds to NFκB and suppressed its function. With inflammatory stimulus, IκB is phosphorylated to be degraded, and free NFκB is transported into nucleus, binds and activates the IL-1β promoter. IL-1β protein is produced as precursor form and processed to mature form protein by Caspase 1 in inflammasome.

IDOL gene consists of IL-1β promoter regulated luciferase fused with Caspase 1 recognition sequence followed by PEST sequence which enhances protein degradation. Inflammatory stimulus activate the transcription of IDOL gene and stabilizes the produced luciferase by the release of PEST sequence processed with Caspase-1 (Fig. B, .C).

< References >
■ wawaki, T., Akai, R., Oikawa, D., Toyoshima, T., Yoshino, M., Suzuki, M., Takeda, N., Ishikawa, T., Kataoka, Y., Yamamura, K. Transgenic mouse model for imaging of interleukin- 1β-related inflammation in vivo. Sci. Rep. vol.5, 17205,(2015).

< Patent >

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Cathepsin E KO mouse

Cathepsin E gene, which encodes aspartic protease related to protein degradation in cellular lysosome is knocked out in this mouse line. Processing of Wnt5a was suppressed, and mammary tumors develop and progress in high frequency.

< References >
■ Carcinogenesis 35: 714-726. 2012
■ Kawakubo, T., Yasukochi, A., Toyama, T., Takahashi, S., Okamoto, K., Tsukuba, T., Nakamura, S., Ozaki, Y., Nishigaki, K., Yamashita, H., Yamamoto, K. Repression of cathepsin E expression increases the risk of mammary carcinogenesis and links to poor prognosis in breast cancer.  Carcinogenesis 35, 714–726, (2014).

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Obesity Resistant Mouse (Rmi1 mutant mouse)

Obesity resistant mouse is a genetrap line discovered from TG Resource Bank. Analysis of phenotype revealed that significant body weight loss and lower blood glucose level in male and female mutant mice. Body weight gain is also suppressed with high-fat diet.

Obesity Resistant Mouse (Rmi1 mutant mouse)

< References >
■ Carcinogenesis 35: 714-726. 2012
■ Suwa, A., Yoshino, M., Yamazaki, C., Naitou, M., Fujikawa, R., Matsumoto, S., Kurama, T., Shimokawa, T., Aramori, I. RMI1 deficiency in mice protects from diet and genetic-induced obesity. FEBS J. 277, 677-686 (2010).

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Eveningness Model Mouse (Clock mutant Mouse)

A mouse that had, as its genetic background, a BALB/c strain that possessed a mutation of the clock gene – one of the gene's related to the biological clock - was repeatedly backcrossed with a mouse of the Jcl:ICR strain. As a result, a "eveningness model mouse," which displays characteristics, mentioned below, that are different from those of an ordinary clockmutant mouse, was obtained.

Given the characteristics mentioned below, this mouse is expected to contribute greatly to, among other things, elucidating abnormal mechanisms of circadian rhythm.

Delayed Circadian Rhythm
When the mouse is raised in a light-dark cycle, the peak of its body temperature and spontaneous activity during the phases of its circadian rhythm appears 2-3 hours later than that of wild-type mouse (hence "eveningness").Delayed Circadian Rhythm
A Long-Cycle Rhythm
When the mouse is raised under conditions of constant darkness, its water-drinking behavior displays about 28-hour cycle (hence "long cycle"). Even if the mouse continues to be raised for over a year, this long-cycle rhythm does not disappear.A Long-Cycle Rhythm

< References >
■ Sei, H,, Oishi, K,, Morita, Y,, Ishida, N. Mouse model for morningness/eveningness. NeuroReport 12, 1461-1464 (2001).
■ Oishi, K,, Miyazaki, K,, Ishida, N. Functional CLOCK is not involved in the entrainment of peripheral clocks to the restricted feeding: entrainable expression of mPer2 and BMAL1 mRNAs in the heart of Clock mutant mice on Jcl:ICR background. Biochem Biophys Res Commun. 298, 198-202 (2002).

< Patent >
■ Patent Application Publication No. 2003-70376

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Atopic dermatitis Model Mouse (IL33 Tg Mouse)

Atopic dermatitis Model Mouse (IL33 Tg Mouse)

Atopic dermatitis and IL33
Atopic dermatitis is a type of inflammation of the skin which main symptom is itchy repeating dermatitis.
The number of patients reaches 10 – 20% of population. The cause is still unknown, although many hypotheses have been presented.
IL33 is an interleukin which localizes in the nuclear of various epithelial cells and endothelial cells, and secreted to extracellular space to activate immune cells including lymphocyte, adipocyte, basophils and eosinophils. IL33 is considered to be involved in allergic diseases such as hay fever, nasal inflammation and asthma, arthritis, diabetes and inflammatory bowel disease. IL33 is also expressed in the skin of atopic dermatitis patients.

IL33 Tg mousee
Dr. Yasutomo Imai and Dr. Kiyofumi Yamanichi produced transgenic mice in which IL33 gene is expressed in the skin under the regulation of skin specific keratin 14 promoter to investigate a role of IL33 in skin. As a result, it was shown that the 100% of transgenic mice spontaneously developed atopic dermatitis after 8 weeks old. The transgenic mice shows itchy dermatitis on body surface especially on face, ears and tails. They also show the infiltration of inflammatory cells into dermis, increased number of adipocytes, increased amount of chemokines, and higher levels of blood IgG and histamine. These observations suggest the mechanism that the increase amount of IL33 in skin activates adipocytes and type II innate lymphoids, resulting increased number of eosinophils causes atopic dermatitis.
Thus, IL33 Tg mice are considered to be a good model which reproduce the status of atopic dermatitis and expected to be useful for development of the treatment method and therapeutic agents targeting this disease.

IL33 Tgマウス

< References >
■ Imai, Y., Yasuda, K., Sakaguchi, Y., Haneda, T., Mizutani, H., Yoshimoto, T., Nakanishi, K., Yamanishi, K.
Skin-specific expression of IL-33 activates group 2 innate lymphoid cells and elicits atopic dermatitis-like inflammation in mice.
Proc. Natl. Acad. Sci. U.S.A. 110, 13921-13026 (2013).

< Patent >
■ Pub. No.:(WO2014178392A1) Atopic dermatitis model animal and use thereof

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